Brooklyn, New York – Researchers at the Polytechnic Institute of New York University (NYU-Poly) and the NYU College of Dentistry (NYUCD) have developed a carrier in their lab that is five times more efficient in delivering DNA into cells than today's commercial delivery methods—reagent vectors. This novel complex is a peptide-polymer hybrid, assembled from two separate, less effective vectors that are used to carry DNA into cells.
Results of their study, "Long Term Efficient Gene Delivery Using Polyethylenimine with Modified Tat Peptide," were published in Biomaterials. The findings were the result of a collaborative research project conducted by Dr. Seiichi Yamano at NYUCD and Dr. Jin Montclare at NYU-Poly. The outcome of the study could help researchers better understand gene function and ultimately improve gene therapy.
Non-viral vectors such as those engineered in this study are used for transfection—the process of introducing foreign genetic material (in this case, DNA called a plasmid) into a cell. The vectors are essentially vehicles that carry the genetic matter into the cell. But transfection is not as easy. Cells are set up to keep things out of the nucleus. Even if the transported plasmid manages to permeate the cellular membrane, the cytoplasm within the cell has safeguards to stop anything from getting into the nucleus.
Traditionally, scientists have engineered viruses to carry out transfection, but viruses are problematic because cells recognize them as foreign and trigger the immune response. Virus transfection is extremely costly and presents numerous difficulties for mass processing. On the other hand, non-viral vectors do not trigger the immune system and are easily manufactured and modified for safe, more effective delivery. Their shortcoming is that they generally are effective only for short periods in transfection, as well as other forms of gene expression.
For this project, Yamano and Montclare paired a modified version of CPP HIV-1 (mTat) with PEI – a non-viral vector particularly effective for delivering oligonucleotides. In combining mTat and PEI, they built a new non-viral vector, more effective than mTat or PEI individually. They tested their reagent vector both in vitro—grown in a Petri dish—as well as for approximately seven months in a living organism--in vivo.
The vector may be used in the future for targeted gene therapy.
In addition to Montclare and Yamano, Drs. Jisen Dai, Shigeru Hanatani, Ken Haku, Takuto Yamanaka, Mika Ishioka and Tadahiro Takayama, all of the NYUCD Department of Prosthodontics; Carlo Yuvienco of the Department of Chemical and Biomolecular Engineering at NYU-Poly; Sachin Khapli of the NYU Abu Dhabi Division of Engineering; and Amr Moursi of the NYUCD Department of Pediatric Dentistry also contributed to this project.
This research was funded in part by the National Science Foundation, the NSF Materials Research Science and Engineering Centers (MRSEC) program, and the U.S. Army Research Office.
The Polytechnic Institute of New York University (formerly the Brooklyn Polytechnic Institute and the Polytechnic University, now widely known as NYU-Poly) is an affiliated institute of New York University, and will become its School of Engineering in January 2014. NYU-Poly, founded in 1854, is the nation's second-oldest private engineering school. It is presently a comprehensive school of education and research in engineering and applied sciences, rooted in a 159-year tradition of invention, innovation and entrepreneurship. It remains on the cutting edge of technology, innovatively extending the benefits of science, engineering, management and liberal studies to critical real-world opportunities and challenges, especially those linked to urban systems, health and wellness, and the global information economy. In addition to its programs on the main campus in New York City at MetroTech Center in downtown Brooklyn, it offers programs around the globe remotely through NYUe-Poly. NYU-Poly is closely connected to engineering in NYU Abu Dhabi and NYU Shanghai and to the NYU Center for Urban Science and Progress (CUSP) also at MetroTech, while operating two incubators in downtown Manhattan and Brooklyn. For more information, visit http://www.poly.edu.
The NYU College of Dentistry(NYUCD), founded in 1865 as the New York College of Dentistry, is the third oldest dental school in the country and the largest comprehensive oral health care center in the world, graduating approximately 8 percent of U.S. dentists annually. In 1925, the College officially merged with New York University, which led to the promotion of research and postdoctoral education. Today, NYUCD is recognized as a leading source for dental care in New York City and a leader in national research rankings and national policy issues in dentistry. NYUCD, a globally focused academic dental center, conducts the most extensive dental public health outreach programs in the world. For more information, visit http://www.nyu.edu/dental.
Journal
Biomaterials